Epidemiological evidence indicates that consumption of alcoholic beverages by smokers increases the risk for head and neck cancers, especially oral cavity cancer. In addition, tobacco chewing and the use of tobacco snuffs have also been implicated as risk factors for the development of oral cancer. Both tobacco and tobacco smoke contain numerous chemicals which have been shown to cause tumors in experimental animals. In particular, the N-nitrosamine fraction contains carcinogens, many of which cause head and neck tumors in experimental animals. Since both tobacco and tobacco smoke are complex mixtures, they contain components which themselves are not tumor initiators but can exert biological effects that can alter the carcinogenic response of tissues to tumor initiators at the metabolic activation step or at any of the steps involved in the carcinogenic process. The proposed series of studies will examine the biological effects of in vitro and in vivo exposure to ethanol and aqueous tobacco extracts on the metabolism of the N- nitrosoamines in hamster cheek pouch epithelial microsomes as well as on the specific content of cytochrome P-450 isozymes involved in xenobiotic metabolism. Defining the metabolic alterations in target tissue metabolism that result from in vitro and in vivo exposure to ethanol and tobacco extracts will allow for rational design of experimental carcinogenicity studies.